Various factors for determining the color of skin or hair have been reported, but among them, the amount or quality of melanin, that is present in the epidermis is considered to contribute to the color of skin or hair to a large extent. That is, color formation in skin or hair is believed to be largely affected when melanin, which is produced in a cell organelle called melanosome in the pigment cells (melanocytes), is transferred to keratinocytes in the epidermis or hair follicles, and spreads over the entirety of the epidermis or hair. The amount of melanin produced by those melanocytes has been known for long as a factor associated with the color of skin, or hair of an individual.
Conventional skin whitening agents have been developed primarily for targeting melanin production in melanocytes. For example, Non-Patent Document 1 reports skin, whitening agents having an action of inhibiting the enzymatic activity of tyrosinase, which is an enzyme involved in the conversion of tyrosine, a melanin precursor, to melanin and thereby suppressing melanin production, such as ascorbic acid, arbutin, and kojic acid.
On the other hand, it has also been reported that depending on the differences in skin color, differences in the form of existence or the state of maturity of melanin in keratinocytes are also recognized (Non-Patent Document 2). That is, a possibility that the melanin dynamics in keratinocytes may be in charge of a certain role in the determination of skin color. In the reports published so far, it has been suggested that a receptor molecule, PAR-2, is involved in the uptake (phagocytosis) of melanin in keratinocytes, and there is a possibility of the control of skin color by regulating the activity of the receptor molecule (Non-Patent Document 3). Furthermore, it has been suggested that protein molecules Dynein and Dynactin participate in the localization of melanin in keratinocytes after melanin is transferred to the keratinocytes Patent Documents 4 and 5). More recently, it has been suggested that a protein molecule, MyoX, which is involved in the formation of a cellular structure called filopodium, is involved in both the transfer of melanin from a melanocyte to a keratinocyte and the transfer of melanin from a keratinocyte to a keratinocyte (Non-Patent Document 6). However, the mechanism of uptake, transport and metabolism by keratinocytes of the melanin (melanosome) produced in melanocytes has not yet been sufficiently elucidated, and the role involving in skin color has not been verified.
Furthermore, recently, it has been suggested, from an investigation using keratinocytes derived from different races, that there are racial differences in the metabolic capacity of melanin that has been incorporated in the keratinocytes (Non-Patent Document 7). This article reports that melanin is prone to be decomposed in Caucasian-derived epidermal cells, based on the results obtained by incorporating a melanin that was labeled with a fluorescent substance into epidermal cells, and then observing the progress of extinction of fluorescence in the epidermal cells. However, nothing is mentioned regarding the mechanism contributing to the decomposition or any particular factor.
CLIP-170, RAB7B, Rubicon, RAB11A, and ATG7 are known as molecules that participate in the transport or localization of vesicles, or in the decomposition or self-digestion of vesicles (Non-Patent Documents 8 to 16). However, it has not been made clear as to whether these molecules are involved in the melanin dynamics in keratinocytes, for example, uptake, transport, localization or accumulation, excretion or decomposition of melanin.